The present invention pertains to medical apparatus, particularly expandable stents, having a surface coating applied over a portion of the apparatus"" surface. In particular, the present invention relates to a generally impermeable surface coating which protects therapeutic materials disposed under the surface coating from the surrounding environment until the release of these materials is desired and achieved through fracture of the surface coating.
While angioplasty has gained wide acceptance, abrupt closure and restenosis have been identified as possible subsequent occurrences. Abrupt closure refers to the acute occlusion of a vessel immediately after or within the initial hours following a dilation procedure. Abrupt closure can result in myocardial infarction if blood flow is not restored in a timely manner. The primary mechanisms of abrupt closures are arterial dissection and/or thrombosis. Restenosis refers to the re-narrowing of an artery after an initial successful angioplasty. Restenosis occurs primarily within the initial six months after angioplasty, and is believed due to the proliferation and migration of the cellular components of the arterial wall.
Endovascular stents are placed in the dilated segment of a vessel lumen to mechanically block the effects of abrupt closure and restenosis. In U.S. Pat. No. 5,514,154, Lau et al. disclose an expandable stent which is relatively flexible along its longitudinal axis. This flexibility facilitates delivery of the stent through tortuous body lumens. Additionally, the stent is stiff and stable enough radially, in an expanded condition, to maintain the patency of a body lumen such as an artery when implanted therein. Such stents have not, however, eliminated abrupt closure and have not eliminated restenosis.
Recent developments have led to stents which attempt to provide anti-thrombogenic and other medications to regions of a blood vessel which have been treated by angioplasty or other interventional techniques. In U.S. Pat. No. 5,464,650, Berg et al. disclose a method for making an intravascular stent by applying to the stent, and in particular to its tissue-contacting surface, a solution which includes a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the solvent. After the solution is applied to the stent, the solvent is then evaporated leaving the polymer/therapeutic agent surface treatment. Berg et al. assert that these devices are capable of providing both short term medication delivery, over the initial hours and days after the treatment, as well as long term medication delivery, over the weeks and months after the treatment.
An ongoing problem with present drug release coatings applied to devices such as stents is achieving a therapeutic concentration of a drug locally at a target site within the body without producing unwanted systemic side effects. Implantation of vascular stents is a prime example of a situation where local therapy is needed with drugs that also produce unwanted systemic side effects. Because the stent is placed within a flowing blood stream, during placement and upon implantation, potential unwanted systemic effects may result from undesirable quantities of the therapeutic substance entering the blood stream. Further, if quantities of therapeutic substance are released into the blood stream during positioning of the stent, less is available for actual local treatment when the stent is expanded, resulting in potential inadequate local dosing. The many attempts to effectuate local drug delivery via endovascular means have failed to address controlling of release of the therapeutic substance systemically during implantation and following implantation.
Therefore, there exists a need in the art for a means and a method for providing local therapy which can sustain high local concentrations of therapeutic drugs at a predetermined site without producing unwanted side effects, such as unwanted quantities of the drugs entering the blood stream. There especially exists a need to provide adequate concentration of therapeutic agents directly to the boundary layer of blood flow near the vessel wall at a targeted treatment area which greatly reduces the systemic side effects and amount of drug needed to achieve a therapeutic result.
The present invention provides a medical device, and a method for manufacturing the medical device, which includes a thin layer overlying a releasable drug or therapeutic substance layer. The thin overlying layer protects the drug layer during positioning and deployment of the medical device within a body lumen. The thin overlying layer is selected to be of a polymeric material and selected thickness which essentially prevents elution of the therapeutic substance until the medical device is placed at a desired location within the body lumen and expanded. The expansion of the medical device produces fissures throughout the overlying layer through which the therapeutic substance elutes. With this design, the therapeutic substance is assured to be applied at the local selected delivery site with substantially reduced systemic effect from the drug entering the blood stream and traveling away from the deployment site.
The present invention is useful in conjunction with local delivery of drugs or therapeutic substances on an expandable stent within the vascular system. The invention may also be utilized in conjunction with drug delivery from balloon catheters or stents for use in other body lumens. The invention is particularly useful when utilizing a water soluble drug or therapeutic substance which tends to dissolve and migrate within a blood or other body fluid environment. It is also beneficial to use the overlying protective coating when the drug is placed on the medical device with a hydrophilic polymeric carrier, which is intended to dissolve and release the drug or therapeutic substance over an extended period of time when the device is placed within the body lumen at a selected site. The second or overlying layer of protective material, which fractures upon expansion of the medical device, is preferably a biodegradable polymer which is absorbed by the body over an extended period of time, but which prevents elution of the drug or therapeutic substance during the time required to place the device within the vessel lumen.
In preferred embodiments of the present invention, the medical device is one which is designed for treating a vessel lumen wall, such as an arterial wall, in conjunction with treating a stenosis at the same location. The medical device preferably includes a body portion having an exterior surface defined thereon with the body portion being expandable from a first position, wherein the body portion is sized for insertion into the vessel lumen, to a second position, wherein at least a portion of the exterior surface of the medical device is in contact with the lumen wall. A preferred medical device includes a first coating disposed over at least a portion of the exterior surface of the body portion of the medical device with the first coating including, at least in part, a drug or therapeutic substance for treating the vessel wall. In preferred embodiments, the first coating includes the drug or therapeutic substance in combination with a polymeric carrier which preferably controls the rate of release of the drug or therapeutic substance over an extended period of time. The therapeutic substance or drug releases from the first coating, in preferred embodiments, in response to contact with fluid within the vessel lumen or at the vessel wall.
Preferred drugs or therapeutic substances which may be incorporated into the first coating or included in the first coating with a polymeric carrier include heparin, antibiotics, radiopaque agents, anti-thrombogenic agents, anti-proliferative agents, anti-angiogenic agents, and combinations thereof. Specific drugs can include taxol, taxol derivatives, colchicine, vinblastine or epothilones, which are classified as anti-proliferative and anti-angiogenic agents. A preferred polymeric carrier for the drug or therapeutic substance is a biodegradable agent which can include polylactic acid, polyglycolic acid, polyethylene oxide, polycaprolactones, polydioxanone, poly(orthoesters), polyanhydrides, polyphosphazenes, and mixtures or copolymers of these polymeric materials. The polymeric material could also be selected to include non-biodegradable polymers such as polyurethane, polysiloxane, polyacrylate and mixtures and copolymers of these polymeric materials.
The present invention includes a second coating preferably overlying at least a substantial portion of the first coating. The second coating includes at least in part a material that is generally impervious to elution of the drug or therapeutic substance therethrough when the body portion of the medical device is in the first position, while being inserted and placed within the lumen. Further, the material of the second coating is preferably relatively inelastic so that the second coating fractures during expansion of the body portion of the medical device to the second position to allow elution of the drug or therapeutic substance through fissures formed through the surface of the second coating. The second coating of the present invention works particularly well in combination with expandable stents or drug delivery balloons. The second coating is preferably a polymeric material which can include polylactic acid, polyglycolic acid, polyanhydrides, polyphosphazenes, poly(orthoesters) and mixtures and copolymers of these polymeric materials. In preferred embodiments, the thickness of the second coating is about 0/01 xcexcm to about 5 xcexcm.
A preferred medical device of the present invention includes a stent which is a generally tubular structure having an exterior surface defined by a plurality of interconnected struts having interstitial spaces therebetween. The generally tubular structure is expandable from a first position, wherein the stent is sized for intravascular insertion, to a second position, wherein at least a portion of the exterior surface of the stent contacts the vessel wall. The expanding of the stent is accommodated by flexing and bending of the interconnected struts throughout the generally tubular structure. The second coating overlying the stent surface which protects the therapeutic substance or drug during placement, fractures upon flexing and bending of the struts on the stent during expansion.
The second coating of the present invention can also be utilized on a medical device, such as a balloon catheter, wherein the second coating is included on at least a portion of the balloon which is expandable from a folded or unexpanded first position to an expanded second position which is adapted for treatment of the vascular lumen wall by contact with at least a portion of the exterior surface of the balloon. The second coating overlying the drug or therapeutic substance is again relatively inelastic so that upon expansion of the balloon, the coating fractures to allow elution of the drug or therapeutic substance through fissures formed in the coating.
Additional features of the invention and the advantages derived therefrom, and the various scopes and aspects of the invention will become apparent from the drawings, the description of the preferred embodiments of the invention, and the claims.